Antischistosomal tetrahydro-γ-carboline sulfonamides

Bioorg Med Chem Lett. 2022 Mar 1:59:128546. doi: 10.1016/j.bmcl.2022.128546. Epub 2022 Jan 12.

Abstract

We discovered tetrahydro-γ-carboline sulfonamides as a new antischistosomal chemotype. The aryl sulfonamide and tetrahydro-γ-carboline substructures were required for high antischistosomal activity. Increasing polarity improved solubility and metabolic stability but decreased antischistosomal activity. We identified two compounds with IC50 values <5 µM against ex vivo Schistosoma mansoni.

Keywords: Antischistosomal; SAR; Sulfonamides; Tetrahydro-γ-carboline.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbolines / chemical synthesis
  • Carbolines / chemistry
  • Carbolines / pharmacology*
  • Dose-Response Relationship, Drug
  • Molecular Structure
  • Schistosoma mansoni / drug effects*
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Carbolines
  • Sulfonamides
  • gamma-carboline